MultiDimensional ClinOmics for Precision Therapy of Children and Adolescent Young Adults with Relapsed and Refractory Cancer: A Report from the Center for Cancer Research

Clin Cancer Res. 2016 Aug 1;22(15):3810-20. doi: 10.1158/1078-0432.CCR-15-2717. Epub 2016 Mar 18.

Abstract

Purpose: We undertook a multidimensional clinical genomics study of children and adolescent young adults with relapsed and refractory cancers to determine the feasibility of genome-guided precision therapy.

Experimental design: Patients with non-central nervous system solid tumors underwent a combination of whole exome sequencing (WES), whole transcriptome sequencing (WTS), and high-density single-nucleotide polymorphism array analysis of the tumor, with WES of matched germline DNA. Clinically actionable alterations were identified as a reportable germline mutation, a diagnosis change, or a somatic event (including a single nucleotide variant, an indel, an amplification, a deletion, or a fusion gene), which could be targeted with drugs in existing clinical trials or with FDA-approved drugs.

Results: Fifty-nine patients in 20 diagnostic categories were enrolled from 2010 to 2014. Ages ranged from 7 months to 25 years old. Seventy-three percent of the patients had prior chemotherapy, and the tumors from these patients with relapsed or refractory cancers had a higher mutational burden than that reported in the literature. Thirty patients (51% of total) had clinically actionable mutations, of which 24 (41%) had a mutation that was currently targetable in a clinical trial setting, 4 patients (7%) had a change in diagnosis, and 7 patients (12%) had a reportable germline mutation.

Conclusions: We found a remarkably high number of clinically actionable mutations in 51% of the patients, and 12% with significant germline mutations. We demonstrated the clinical feasibility of next-generation sequencing in a diverse population of relapsed and refractory pediatric solid tumors. Clin Cancer Res; 22(15); 3810-20. ©2016 AACR.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm
  • Exome Sequencing
  • Female
  • Genomics* / methods
  • Germ-Line Mutation
  • Humans
  • Infant
  • Male
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasms / diagnosis
  • Neoplasms / genetics*
  • Neoplasms / therapy*
  • Polymorphism, Single Nucleotide
  • Precision Medicine* / methods
  • Recurrence
  • Young Adult

Substances

  • Biomarkers, Tumor